Carcinogenic potential of processed meat and plant-based meat alternatives in the A/J Min/+ mice model (Mus musculus).

Colorectal cancer (CRC) is one of the most common cancers both worldwide, and in Norway, with high mortality rates. The risk of developing CRC has been associated with diet and lifestyle, where, according to IARC, red and processed meat are classified as probably carcinogenic and carcinogenic to humans, respectively. Multiple theories of the relationship between CRC and meat have been studied, however, the causality and underlying mechanisms are yet to be documented. CRC arises mostly by somatic mutations (70%), with a mutation in the tumor suppressor gene adenomatous polyposis coli (APC) playing an initiating role of carcinogenesis. Some cases are however caused by germline mutations in the APC gene, such as the inherited condition familial adenomatous polyposis (FAP). Multiple intestinal neoplasia (Min/+) mice model has previously been established as a human model for studies on colorectal carcinogenesis. The overall aim of the present study was to investigate the carcinogenic potential of experimental diets prepared from commercially available processed meat –and plant-based meat alternatives in the A/J Min/+ mouse model. An inbred colony of A/J mice heterozygous for the Min trait (Min/+) were included in this study and were randomly recruited into 4 experimental groups at 4 weeks of age. The experimental diets were based on commercial processed meat -and plant-based meat alternative products (hot dog, hamburger and vegan burger). The mice were exposed to experimental diets for 9 weeks before termination. Lesions in the small intestine (SI) and colon were scored after staining and fixation using a light microscope. We found a carcinogenic initiating potential of the hot dog in the SI. The reference diet exhibited a promoting effect on the SI and colon, as well as an initiating potential on the colon. However, a promoting potential on the colon was also found in the vegan diet. In the colon, gender-specific differences in carcinogenic potential were found. The hot dog diet and the reference diet exhibited an initiating potential in males and females, respectively. Moreover, the vegan diet showed a promoting potential in males. Altogether, we revealed a carcinogenic potential of not only processed meat products but also processed meat alternatives. However, further research is needed to understand the complex interplay of dietary, genetic and lifestyle factors on carcinogenesis and the underlying mechanisms

"Opptrapping og samhandling". Hva er status for det psykiske helsefeltet etter samhandlingsreformens tilblivelse? Et kommunalt lederperspektiv på utfordrende pasientgrupper og samhandling med fastleger og spesialisthelsetjeneste

Oppgaven omhandler de utfordringer kommunalt psykisk helsetjeneste har med utfordrende pasientgrupper etter samhandlingsreformens tilblivelse og hvordan koordineringen av behandlingsforløp fungerer. 6 kommunale lederer er intervjuet semi-strukturert. Samhandlingstriangelet kommune, fastlege og spesialisthelsetjeneste blir teamtisert gjennomgående i oppgaven. Resultatene viser at det er stor er stor variasjon i tilgjenglighet og kvalitet i behandlingsforløp og koordinering

Modulation of [mu]-mediated antinociception by [delta] agonists in the mouse: selective potentiation of morphine and normorphine by [D-Pen2, D-Pen5]enkephalin

The effect of the [delta]-selective agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) on the antinociception produced by intracerebroventricular (i.c.v.) administration of the [mu] agonists morphine, [D-Ala2, NMePhe4,Gly-ol5]enkephalin (DAGO), [NMePhe3,D-Pro4]morphiceptin (PLO17), [beta]-endorphin, phenazocine, etorphine and sufentanil was studied in mice. Only the antinociceptive effects of morphine and normorphine were modulated by i.c.v. coadministration of a dose of DPDPE which did not prodice any significant antinociception alone. Both the morphine and normorphine dose-response lines were displaced to the left in the presence of DPDPE. The [delta]-selective antagonist ICII74,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH) (where Aib is [alpha]-aminoisobutyric acid) blocked the modulation of morphine antinociception by DPDPE. ICI 174,864 alone failed to produce either a significant increase or decrease of morphine, phenazocine, etorphine or [beta]-endorphin antinociception. The results of the present study provide support for the hypothesis that the enkephalins may function to modulate antinociception produced at the [mu] receptor; such modulation may come about via the existence of an opioid [mu]-[delta] receptor complex. The [mu] receptors existing in such a complex may be selectively activated by morphine and normorphine, but not the other [mu] agonists studied here. Thus, the enkephalins may function both to directly initiate, as well as to modulate, some forms of supraspinal [mu] receptor-mediated antinociception.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27888/1/0000302.pd

Opioid antinociception in a rat model of visceral pain: systemic versus local drug administration

Antinociceptive effects of systemically or locally administered opioid mu, kappa and delta agonists were evaluated in a rat model of visceral pain. Resiniferatoxin (RTX, 3 nmol), a capsaicin-like mutant, produced abdominally directed grooming behavior after direct administration into the urinary bladder (intravesical, Lves.) by indwelling cannula. Systemic (s.c. or i.p.) pretreatment with the mu agonists morphine or [D-Ala2, NMePhe4, Gly-ol]enkephalin (Damgo), the kappa agonists trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide (U50,488) or [5R-(5,7,8-beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro[4,5]dec - 8-yl]-4-benzofuranacetamide (CI-977), or the nonpeptidic delta agonist (+/-)-4-((alpha-R*)-alpha-((2S*,5R(*)-4-Allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N, N-diethylbenzamide (BW373U86) dose-dependently decreased RTX-induced abdominal licking; such antinociception was selectively blocked by the appropriate receptor-selective antagonists beta-funaltrexamine (mu), nor-binaltorphimine (kappa) and naltrindole (delta). Local (i.ves.) BW373U86, [D-Ala2,Glu4]deltorphin (DELT II) and Cl-977 also significantly decreased RTX-induced licking. Intracerabroventricular quaternary naloxone partially blocked the effects of systemic morphine, but not that of CI-977 or BW373U86. Intraperitoneal quaternary naloxone blocked the effect of local and systemic BW373U86 but not that of local or systemic CI-977; systemic morphine was partially blocked. Thus, systemic mu, kappa and delta agonists all produced antinociception against a novel visceral chemical stimulus in the rat. Local CI-977 also produced antinociception, but the only compound clearly acting at peripheral opioid receptors was BW373U86, a delta agonist. This study suggests that opioid delta receptors may be present on bladder nociceptive afferents and may be activated for production of peripheral analgesia

Role of steric interactions in the delta opioid receptor selectivity of [d-Pen 2 , d-Pen 5 ]enkephalin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71860/1/j.1399-3011.1988.tb00919.x.pd